There is a critical need for improved contraceptive methods both in the U.S. and worldwide. Nearly half of all pregnancies in the U.S. are unintended, and globally there are over 85 million unintended pregnancies each year. Unintended pregnancies represent a $20B+ cost burden to the health system across the federal and state levels in the U.S. alone. The majority of unintended pregnancies are concentrated in women who are non-users of contraception, underscoring the need for contraceptive methods with greater user acceptability and compliance. Through direct interviews with over a hundred prescribers, experts and key opinion leaders in the contraceptive field, we have confirmed that there is a major unmet need for an effective, reversible, non- hormonal and non-coitally associated contraceptive method. Currently, the only non-hormonal option that is also non-coitally associated is the copper intrauterine device, which often leads to heavy menstruation, significant cramping and abdominal pain. Inspired by nature, whereby some infertile woman can produce antibodies that bind surface antigens on sperm that block sperm penetration through her cervical mucus, we have investigated a fully human monoclonal antibody (mAb) that can quickly bind an antigen present only on the surface of sperm and other cells originating from the male reproductive tract. We refer to this mAb as a human contraceptive antibody (HCA). Importantly, the antigen appears to be ubiquitous on human sperm, as all semen samples from 100 men spanning diverse demographics were agglutinated by the prototype HCA, with >90% of sperm agglutinated in fresh semen within seconds. We have verified in vivo contraceptive effectiveness of a rabbit sperm-binding mAb similar to HCA, where vaginal delivery of this sperm-binding mAb reduced fertilized eggs by 95%. Due to notorious variations in the functional performance of mAb produced in different cell systems, to advance our goal of non-hormonal contraception based on HCA released from an intravaginal ring (IVR) throughout the fertility window, the next phase in the development cycle is to produce the same mAb using a scalable process. In Aim 1 of this proposal, we seek to develop a high secreting cell line of HCA using DG44 Chinese Hamster Ovary cells, a frequently used platform in industry for scalable production of biologics. We will verify that HCA produced by stable DG44 cells maintains the same sperm- binding affinity and sperm agglutination and trapping potency compared to HCA produced using transient production methods. In Aim 2, we will incorporate HCA into Mucommune's proprietary capsule-IVR design, verify that we can release HCA into human cervicovaginal mucus for at least 28 days, and measure the sperm agglutination and trapping potencies of the released HCA. Our long-term goal is to develop a shelf-stable non- hormonal contraceptive IVR. Successful completion of the Phase I aims will lead to a Phase II proposal verifying we can sustain effective contraceptive concentrations in macaques, and further develop the manufacturing platform in preparation for pre-IND toxicity and efficacy studies.